After men reach the age of 40 years, testosterone levels decline approximately 1 percent per year. This decline can lead to age-associated testosterone deficiency, which is present in 30 percent of men 55 years or older. Testosterone levels have also been shown to decline with severe illnesses, malnutrition, or drug use, particularly corticosteroids and alcohol. Men with age-associated hypogonadism have total testosterone levels of 150 to 350 ng per dL (5.20 to 12.13 nmol per L). Symptoms related to hypogonadism include diminished muscle mass and strength, anorexia, decreased libido, decreased bone mineral density, fatigue, dysphoria, and irritability.

Several studies have examined the relationship between testosterone levels and depression, but the results have been inconsistent. In addition, studies evaluating the use of testosterone in the treatment of depression in men with low testosterone levels have not yielded consistent results. Shores and associates conducted a study to determine if hypogonadal men have an increased incidence of depressive illness compared with men who have normal testosterone levels.

The trial design was a historical cohort study using computerized medical records from a regional veterans’ health care system. Inclusion criteria were an age of 45 years or older, at least two visits to the medical center each year, available baseline and follow-up testosterone levels separated by at least one year, and stable testosterone levels. Subjects were excluded if they had a diagnosis of depressive illness or were treated with anti-androgens. The researchers used a total testosterone level of 200 ng per dL (6.93 nmol per L) or less or a free testosterone level of 0.9 ng per dL (0.03 nmol per L) or less as their threshold for diagnosing hypogonadism.

The next step was to identify patients who had a clinically diagnosed depressive illness during the past two years. Demographic information and comorbidities were extracted from the records. A manual record review was performed by a person who was blinded to the testosterone levels. A psychiatrist who also was blinded to the testosterone levels then conducted a comprehensive review of the patient records to identify those with depressive illnesses.

There were 278 men who met the inclusion and exclusion criteria, had consistent normal or low testosterone levels at baseline and during the two-year follow-up, and did not have a history of depressive illness. The incidence of diagnosed depressive illnesses was significantly higher in men who had testosterone levels that met the criteria for hypogonadism (21.7 percent) than in men who had normal testosterone levels (7.1 percent).

The data were analyzed using Cox proportional hazards regression models to examine the association between hypogonadism and time to depression. The unadjusted hazard ratio for depression in men with hypogonadism was 3.5. After adjustment for all covariates, including age, race, number of clinic visits, alcohol use, prostate cancer, and overall medical comorbidity, the hazard ratio was 4.2.

The authors conclude that men with hypogonadism had an increased incidence of depressive illnesses and a shorter time to diagnosis of depression. They add that their study does not address the issue of using testosterone to treat or augment treatment for depression in men with hypogonadism.